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    Increased IgA Expression in Lung Lymphoid Follicles in Severe Chronic Obstructive Pulmonary Disease

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    A study directed by Maha-Zohra Ladjemi, team Chiche-Burgel

    Chronic obstructive pulmonary disease (COPD) is associated with aberrant immune and structural responses of the airways to inhaled toxics.

    In collaboration with the team of Jean-Daniel Chiche and Pierre-Régis Burgel (Institut Cochin), the team of Charles Pilette (Université Catholique de Louvain, Bruxelles) has recently published an article in the American Journal of Respiratory and Critical Care Medicine, suggesting exacerbated type A Immunoglobulin (IgA) immune responses against foreign (e.g., microbial) and/or self-antigens in severe disease.

    This study demonstrates upregulated IgA expression in lung lymphoid follicles from patients with severe COPD. IgA is upregulated also in the lungs from mice infected by Pseudomonas aeruginosa but not in mice exposed to cigarette smoke, suggesting an important role of chronic infection in the induction of IgA responses in severe COPD.

    COPD is often associated with chronic bacterial infections. Accumulation of B cells and lymphoid follicles (LFs) has been described in COPD airways, but the functional status of lung B cells remains poorly known. The aim of this study was to characterize LFs for expression of IgA, the main mucosal antibody.

    The presence of B cells and LFs, including intrafollicular IgA expression and IL-21, were determined in the lung from patients with COPD (n = 37) versus control subjects (n = 34) by immunohistochemistry. We also evaluated follicular IgA responses in the lungs from mice infected with Pseudomonas aeruginosa (PAO1) (n = 10 per group) and in smoking mice.

    Whereas in smokers B-cell numbers slightly increased, robust increases in B-cell and LF numbers (mainly in distal airways) were only observed in severe COPD. Most follicular B cells were IgM+ (70-80%), but IgA+ (and not IgG+) B-cell numbers were increased in LFs from severe COPD compared with control subjects (twofold, 44.7% vs. 25.2%), and this was significant in distal but not proximal airways. The presence of IgA+ LFs was correlated with the severity of the disease. Moreover, follicular IgA expression was associated with expression of IL-21, which was very potent to activate immunoglobulin production in vitro.

    Finally, follicular IgA response was also observed in PAO1-infected mouse lungs (figure), but not after cigarette smoke exposure.

    This study shows that IgA production occurs in peribronchiolar LFs from severe COPD patients, where IL-21-producing T cells are present, and presumably represents a feature of exacerbated mucosal adaptive immune responses against microbial and/or self-antigens.

    (A)

    Sterile beads

    (B)

    Pseudomonas aeruginosa

    IgA expression in lung tissue from Pseudomonas infected mice.
    Representative IgA staining (brown) and hematoxylin counterstaining (blue)
    in lung tissue from mice instilled with (A) sterile beads or
    (B) Pseudomonas aeruginosa (PAO1)-infected mice respectively.

     

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    Ladjemi MZ, Martin C, Lecocq M, Detry B, Nana FA, Moulin C, Weynand B, Fregimilicka C, Bouzin C, Thurion P, Carlier F, Serré J, Gayan-Ramirez G, Delos M, Ocak S1,10, Burgel PR, Pilette C. Am J Respir Crit Care Med. 2019. doi: 10.1164/rccm.201802-0352OC.

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